What is the recommended dose of streptokinase for the treatment of myocardial infarction (MI)?

Streptokinase Dosing in Myocardial Infarction

The recommended dose of streptokinase for acute myocardial infarction is 1.5 million units administered intravenously over 30-60 minutes, initiated as soon as possible after symptom onset. 1, 2

Standard Dosing Regimen

• Administer 1.5 million units of streptokinase intravenously over 30-60 minutes for patients presenting with ST-segment elevation myocardial infarction 1, 2
• The infusion should be diluted in 100 mL of 5% dextrose or 0.9% saline 2
• Treatment should be initiated as soon as possible, ideally within 12 hours of symptom onset, though benefit is greatest when given within 6 hours 2, 1

Timing Considerations

• Streptokinase should be considered when primary PCI cannot be performed by an experienced team within 120 minutes of first medical contact 1
• Reperfusion rates are significantly higher when administered within 6 hours (89.3%) compared to 6-12 hours (50%) after symptom onset 3
• The standard 30-60 minute infusion time appears equally effective, with no significant difference in patency rates between 30-minute and 60-minute infusions 4

Mandatory Adjunctive Antiplatelet Therapy

All patients receiving streptokinase must receive aspirin and clopidogrel unless contraindicated:

• Aspirin: 150-325 mg orally (chewed, non-enteric coated) or 250-500 mg IV if oral administration is not possible 1, 2
• Clopidogrel: Loading dose of 300 mg orally if age ≤75 years, followed by 75 mg daily maintenance dose; for patients >75 years, start with 75 mg daily without loading dose 1, 2
• The benefits of aspirin and streptokinase are additive and independent 2, 1

Anticoagulation Requirements

Anticoagulation must be administered with streptokinase, with fondaparinux being the preferred agent:

First-Line Option:

• Fondaparinux: 2.5 mg IV bolus followed by 2.5 mg subcutaneous once daily (preferred with streptokinase based on OASIS-6 trial superiority) 1, 2

Alternative Options:

• Unfractionated heparin: 60 U/kg IV bolus (maximum 4,000 U) followed by 12 U/kg/hour infusion (maximum 1,000 U/hour) for 24-48 hours, targeting aPTT 50-70 seconds or 1.5-2.0 times control 1, 2, 5
• Enoxaparin (for patients <75 years without renal dysfunction): 30 mg IV bolus followed by 1 mg/kg subcutaneous every 12 hours; for patients ≥75 years, omit IV bolus and use 0.75 mg/kg subcutaneous 1, 2

Important caveat: Unlike fibrin-specific agents (alteplase, tenecteplase), there is limited evidence that heparin beyond aspirin provides additional benefit with streptokinase, though current practice supports its use 2

Monitoring for Reperfusion

Monitor for clinical evidence of successful reperfusion at 60-90 minutes:

• Relief of chest pain 1
• Reduction of ST-segment elevation by ≥50% 1, 4
• Maintenance of hemodynamic and electrical stability 1
• Presence of reperfusion arrhythmias (ventricular tachycardia or accelerated idioventricular rhythm) 4

Post-Thrombolysis Management

• All patients should be transferred to a PCI-capable center following fibrinolysis 1
• Angiography with a view to revascularization is recommended between 3-24 hours after successful fibrinolysis to avoid the early prothrombotic period while minimizing reocclusion risk 1, 2
• If evidence of failed fibrinolysis or reocclusion occurs, immediate angiography is indicated 2

Critical Contraindications and Warnings

Absolute contraindications include: 2

• Hemorrhagic stroke or stroke of unknown origin at any time
• Ischemic stroke within preceding 6 months
• Active internal bleeding or known bleeding disorder
• Recent major trauma/surgery/head injury (within 3 weeks)
• Aortic dissection

Streptokinase-specific contraindication:

• Prior administration of streptokinase or anistreplase at any time (antibodies persist for at least 10 years and can impair activity and increase allergic reaction risk) 2, 1, 2

Common Adverse Effects and Management

• Hypotension commonly occurs with streptokinase administration and should be anticipated 1, 2
• Bleeding complications occur in 4-13% of patients 1
• Intracranial hemorrhage occurs in 0.9-1.0% of patients, with higher risk in patients with lower weight, female sex, previous cerebrovascular disease, and hypertension on admission 1
• Severe allergic reactions are rare, though mild reactions (chills) can occur 1, 3

Important Clinical Pitfalls

• Never re-administer streptokinase due to persistent antibody formation; use alteplase or reteplase for repeat thrombolysis if needed 2, 1
• Do not delay treatment waiting for cardiac biomarkers; ECG criteria (ST-segment elevation or new LBBB) are sufficient to initiate therapy 2
• Fibrin-specific agents (tenecteplase, alteplase, reteplase) are generally preferred over streptokinase when available due to better safety profiles 1
• Continue anticoagulation for minimum 48 hours, preferably for duration of hospitalization up to 8 days, or until revascularization 1, 5